I. Field of the Invention
Embodiments of this invention are directed generally to virology, medicine, and viral therapeutics. Certain embodiments are directed to viral production processes.
II. Background
Oncolytic viruses (OVs) are replicating therapeutics that have been designed or selected to specifically grow in and kill tumor cells. Several groups are in the early stages of commercialization based upon pre-clinical animal models and early clinical data in humans. However, a challenge that still faces the field is to make large scale pharmaceutical grade virus for delivery to patients. Viruses are a biological entity rather than a synthesized drug, thus the manufacturing process involves the production of viruses within cells and the subsequent removal of contaminating cellular debris while maintaining the infective potency. To date, the majority, if not all, commercial manufacturing of vaccinia virus products for human use has been as vaccines in non-human cell cultures. In general for a vaccine application, patients receive low doses of viruses in a local site (often intramuscular) where contaminating cellular proteins may actually serve as an adjuvant to increase the immunogenicity of the preparation. In contrast, for oncolytic virus therapeutics, the doses of viruses needed are up to a million times greater than for vaccine application and may be administered intravenously, intracranially, intraperitoneally or by direct tumor injections. In the case of OVs it is critical to be able to manufacture large quantities of virus which is devoid of contaminating non-human cellular debris. Furthermore, vaccinia viruses are envelope viruses that incorporates host cell protein in the viral membranes. Incorporation of human proteins in the virus envelope will increase its ability to travel without being detected by the human host immune system.
There remains a need for additional methods and composition for large scale oncolytie virus production.